Bioreactor Engineering
Outline of Lecture
1. Bioreactor configurations
2. Bioreactor operation modes
3. Practical considerations for
bioreactor design
What is a bioreactor?
Bioreactor: device, usually a vessel, used to direct the activity of a
biological catalyst to achieve a desired chemical transformation.
Fermenter: type of bioreactor
in which the biocatalyst is a
living cell.
Pre-filtration
Input
Nutrients tank
Waste
Recycle
Product
Bioreactor
Product
separation & purification
Challenges in Bioreactor Design
1. Aerobic bioreactor: Need
adequate mixing and
aeration
2. Anaerobic bioreactor: no
need for sparging or
agitation
Bioreactor Configurations
- 1. Stirred tank
Mixing method: Mechanical
agitation
•Baffles are usually used to
reduce vortexing
• Applications: free and
immobilized enzyme
reactions
•High shear forces may
damage cells
•Require high energy input
Bioreactor Configurations
- 2. Bubble column
Mixing method: Gas
sparging
• Simple design
•Good heat and mass
transfer
•Low energy input
Gas-liquid mass transfer
coefficients depend largely
on bubble diameter and gas
hold-up.
Bioreactor Configurations
- 3. Airlift reactor
Mixing method: airlift
• Compared to bubble
column reactors, in an
airlift reactors, there
are two liquid steams:
up-flowing and downflowing steams. Liquid
circulates in an airlift
reactor as a resutl of
density difference
between riser and
downcomer.
Bioreactor Configurations
- 4. Packed-bed reactor
Packed-bed
reactors are used
with immobilized
or particulate
biocatalysts.
Medium can be
fed either at the
top or bottom and
forms a
continuous liquid
phase.
Bioreactor Configurations
- 5. Trickle-bed reactor
The trickle-bed
reactor is another
variation of the
packed bed
reactors.
Liquid is sprayed
onto the top of the
packing and
trickles down
through the bed in
small rivulets.
Bioreactor Configurations
- 6. Fluidized bed reactor
When the packed beds
are operated in upflow
mode, the bed expands
at high liquid flow rates
due to upward motion
of the particles.
Bioreactor Operation Modes
-1. Batch Operation
A batch bioreactor
is normally
equipped with an
agitator to mix the
reactant, and the
pH of the reactant
is maintained by
employing either
buffer solution or a
pH controller
Change of
Cs with time,
t
•A foam breaker may be installed to disperse foam
dCs
rmax CS
r

dt
K m  CS
Batch
operation with
stirring
Cs 0
K m ln
 Cs 0  Cs   rmax t
Cs
Bioreactor Operation Modes
-2. Plug-flow mode
In a plug-flow
reactor, the
substrate enters
one end of a
cylindrical tube
with is packed with
immobilized
enzyme and the
product steam
leaves at the other
end.
An ideal plug-flow reactor can
approximate the long tube,
packed-bed and hollow fiber or
multistaged reactor
F, Cs0
t=0
F, Cs
V
V

F
Residence
time
Continuous
operation without
stirring
Cs 0
K m ln
 Cs 0  Cs   rmax t
Cs
Bioreactor Operation Modes
-3. Continuous stirred-tank
A continuous
stirred-tank reactor
(CSTR) is an ideal
reactor which is
based on the
assumption that
the reactants are
well mixed.
F, Cs0
F, Cs
V
Continuous
operation with
stirring
Bioreactor Operation Modes
-3. Continuous stirred-tank reactor-Con.
Mass balance of substrate:
F, Cs0
Input - Output  Consumptio n  Accumulati on
F, Cs
V
dCs
FCs 0  FCs  rsV  V
dt
dC s
0
Steady state:
dt
Michaelisrmax C S
Menten rate: r  K  C
m
S
rmax Cs
FCs 0  FCs  V
0
K m  Cs
Bioreactor Operation Modes
-3. Continuous stirred-tank reactor-Con.
Mass balance of substrate:
F, Cs0
F, Cs
rmax Cs
FCs 0  FCs  V
0
K m  Cs
V
rmax Cs
F

V Cs 0  Cs K m  Cs 
F 1

V 
rmax Cs
Cs   K m 
Cs 0  Cs
Practical Issues for Bioreactors
- Temperature Control (Heat Load)
Heat load: Heat load is determined by energy balances
Heat production rate:
q  V    C 
1
Ykcal
Popular
method
q : heat production rate, kcal/ls
V: reactor liquid volume, l
: specific growth rate, s-1
C: biomass concentration (g/l)
Ykcal: a yield coefficient given as
grams of cells formed per kcal energy
released, g cells/kcal
Practical Issues for Bioreactors
-Temperature control (heat transfer)
Heat transfer surface area:
1. Low in (a) external jacket and (b) external coil for small reactors
2. High in (c) internal helical coil and (d) internal baffle coil for large reactors
3. Easily adjustable in (e) a separate external heat exchange unit
Difficult to clean
Easily fouled by cell
growth on the
surface
No cleaning problem
• Sterility
requirement
• Shear forces
imposed on cells
• Depletion of
Practical Issues for Bioreactors
-Agitation (gas transfer)
1. Biological reactions almost invariably are three-phase reactions
(gas-liquid-solid). Effective mass transfer between phases is often
crucial. For example, for aerobic fermentation, the supply of
oxygen is critical.
The equation governing the oxygen transfer rate is:

J A  K l C  C Ag
*
A

C A*  PAg H
Agitation:
•Mechanical stirring (for small reactors, and/or viscous liquids,
low reaction heat)
•Air-driven agitation (for large reactors and/or high reaction heat)
Practical Issues for Bioreactors
- Foaming removal
1. Mechanical foam
breaker (a
supplementary
impeller)
2. Chemical antifoam
agents (may
reduce the rate of
oxygen transfer)
Practical Issues for Bioreactors
- Other issues
1. Aseptic operation (3-5% of fermentations in
an industrial plant are lost due to failure of
sterilization.
2. Construction materials (glass for small
bioreactors, e.g., < 30 liters and corrosionresistant stainless steel for large reactors)
3. Sparage design (three designs: porous, orifice
and nozzle)
4. Evaporation control due to dry air input
Summary of Lecture
1. Bioreactor configurations
2. Bioreactor operation modes
3. Practical considerations for
bioreactor design